- After barely surviving prison, the demented Firefly clan go on the run, unleashing a whole new wave of murder, madness and mayhem.
- After being imprisoned for 10 years, the "Devil's Rejects" are back at it again. Otis (Bill Moseley) escapes prison, meets Winslow (Richard Brake), and devises a plan to get his sister Baby (Sheri Moon Zombie) out too. The Rejects make their way down the road and into Mexico, killing countless people on their way. They find a place to stay, but are soon bombarded with a large group of killers- killers who are after these Three From Hell. Only one group can come out alive, and with the experience these three have, it'll just have to be one great killing joyride.
- After surviving a furious shootout with the police, Baby Firefly, Otis Driftwood and Captain Spaulding are behind bars. But pure evil cannot be contained. Teaming up with Otis' half-brother Winslow "Foxy" Coltrane (Richard Brake), the demented Firefly clan are back to unleash a whole new wave of death and depravity. A firestorm of murder, madness and mayhem will be unleashed in this terror ride to hell and back.—Aaron Kyle
- Needless to say--after escaping death by the skin of their teeth during the blood-soaked shoot-out in The Devil's Rejects (2005)--the murderous trio of sadists, Otis, Baby, and Captain Spaulding, are now left to rot in jail for the rest of their lives. However, evil knows no boundaries, and as the unrepentant mass-murderers miraculously escape from prison, they reunite with Otis' half-brother, Winslow Foxworth, to pick up where they left off, brutalising, once more, the unfortunate ones who stand in their way. Now, a dusty village somewhere in Mexico seems like the perfect refuge; nevertheless, there, too, death, and the brutish henchmen of a powerful assassin, follow the Fireflies. Who shall live, and who shall die in the Day of the Dead?—Nick Riganas
- The film opens with news reports covering the events at the end of the prior film. The reports also reveal that Baby, Otis, and Captain Spaulding miraculously survived being shot and that they will be tried for their crimes. The trial is widely covered and becomes very popular, with many people protesting that the trio are innocent or were only fighting against the system. All three are found guilty and are sentenced to life in prison. Captain Spaulding is executed by lethal injection in prison, however Otis is reunited with his half-brother Winslow Foxworth "Foxy" Coltrane. The two manage to escape from jail during some outside prison work and in the process kill Rondo, who was on the same work crew but did not recognize Otis. Meanwhile Baby unsuccessfully seeks parole, as her mental state has greatly deteriorated since incarceration.
Once free Otis and Foxy begin planning to free Baby from prison. To accomplish this they take the family and friends of Warden Virgil Dallas Harper hostage, demanding that he help Baby sneak out of prison or they will murder everyone. Harper follows their commands and sneaks Baby out of prison by disguising her as a guard, however Otis and Foxy still kill everyone. Now united, the three are undecided as to what to do next but eventually decide to flee to Mexico, a decision that is made more pressing due to the unstable actions of Baby.
Otis, Baby, and Foxy manage to successfully travel to a small town in Mexico that is celebrating the Day of the Dead and hole up in the town's only hotel. They briefly worry about being recognized but dismiss these concerns, unaware that the hotel's owner has recognized them and has alerted Rondo's son Aquarius to their location. The owner keeps them occupied by the celebration and local prostitutes, so as to keep them from moving to another area. The following morning Baby bonds with a local worker, Sebastian, who notices Aquarius's arrival. He warns Baby of the danger before running to warn Otis, just as Aquarius's men break into the whorehouse. Otis and Sebastian manage to hold them off until Foxy arrives and rescues them, after which Otis separates from them to find and kill the hotel owner. During this time Baby manages to kill several of Aquarius's men using a bow and arrow set she took from Harper's house. Eventually Foxy and Baby are captured by Aquarius, who uses them to draw Otis out into the open.
Otis and one of Aquarius's men have a knife fight while Sebastian, who had been shot and left for dead during Foxy and Baby's capture, sneaks up and silently frees Otis's kin. This enrages Aquarius, distracting his man in the knife fight and allowing Otis to gain the upper hand. He, Baby, and Foxy manage to overpower Aquarius, however Sebastian is shot and killed in the process. The film ends with the trio immolating Aquarius before walking off into the town.
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