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Sissy, Missy, and Chrissy are the main antagonists in the movie, Jay and Silent Bob Strike Back.
The fourth member of their team is Justice, who falls for Jay and reluctantly convinces him and Silent Bob to create a diversion while they rob a diamond exchange in Boulder, Colorado. At the film's climax, Justice abandons the other three and turns herself and the other girls in for a reduced sentence.
After getting a restraining order from Randal Graves for selling drugs outside the Quick Stop, Jay and Silent Bob find out from Brodie Bruce that Bluntman and Chronic, the comic book based on their likenesses, has been adapted into a film in production by Miramax Films. In response, Jay and Silent Bob sue Holden McNeil, the co-writer of Bluntman and Chronic for the royalties of the film. However, Holden tells Jay and Silent Bob that he sold his part of the creative and publishing rights of the comic over to his former friend Banky Edwards. Upon learning of the film, as well as the negative reaction it has received so far on the Internet, the two set out on a quest to Hollywood, to prevent the film from being made and tainting their image, or at the very least receive the money from the royalties owed to them.
On the way, they befriend an animal liberation group, consisting of four women: Justice, Sissy, Missy, and Chrissy; and one man, Brent, who they had picked up for the cause. It is revealed that the organization is a mere front; Brent is a bait, intended as a diversion by freeing an animal from a testing laboratory while the girls rob a diamond depository nearby. Jay tricks Brent and throws him out of the van in order to get closer to Justice, with whom he is smitten. Justice, who becomes close to Jay and Silent Bob (particularly the former), reluctantly accepts the two as the new suckers for the thieves.
While the girls are robbing the diamond depository they accidentally set off the alarm, prompting them to break the glass and steal the diamonds. While this is going on Jay and Silent Bob free the animals and take an orangutan named Suzanne with them. The two men escape outside to see the police arriving and their getaway van exploding, which they believe has killed the girls.
The police officers then find and watch footage of a video Sissy recorded of Jay making opprobrious remarks about "the clit", claiming to be "the Clit commander". The literature accompanying the tape says that "Clit" is an acronym for Coalition for the Liberation of Itinerant Tree-Dwellers. Willenholly blindly finds this as an act of terrorism and calls for police support to hunt down what he considered "the two most dangerous men on the planet."
Having escaped the law, Jay and Silent Bob once again resume their quest to reach Hollywood. The two arrive in Hollywood and find themselves in the background of an E! News newscast about their online threat against Miramax. Justice watches the news and takes the diamonds to Hollywood to set things right. Marshal Willenholly learns of their mission to reach Hollywood and also leaves to find them.
After a long chase with studio security Willenholly arrives to capture Jay and Silent Bob, but Justice arrives to save them. Justice admits that the CLIT organization was not real and that the two were used as a diversion while she, Missy, Sissy and Chrissy, were stealing jewels. As the rest of jewel thieves arrive to get their diamond back, a climactic final battle ensues, after which Jay and Silent Bob get their royalties to the film from Banky, and Justice turns herself and her former team in to Willenholly in exchange for a shorter sentence and letting Jay and Silent Bob go.
The film ends with Jay and Silent Bob spending their royalty they earned to locate everyone who expressed negative opinions on the internet about the movie and characters, ranging from kids to clergy, and traveling to their towns to beat them up. The scene then cuts to everyone leaving a movie theater, having just watched the Bluntman and Chronic movie and expressing negative reception. Jay and Silent Bob, with Justice and Willenholly, then go across the street to enjoy a performance from Morris Day and The Time.