X-Men: The Last Stand (also known colloquially as X-Men 3 or X3) is a 2006 superhero film and the third in the X-Men series. Director Brett Ratner took over when Bryan Singer dropped out to direct Superman Returns. The Last Stand revolves around a "mutant cure" that causes serious repercussions among mutants and humans, and on the mysterious resurrection of Jean Grey. The film is loosely based on two X-Men comic book story arcs: writer Chris Claremont's and artist John Byrne's "The Dark Phoenix Saga" and writer Joss Whedon's and artist John Cassaday's six-issue "Gifted" arc.

Following Singer's departure, the director's position was offered to Darren Aronofsky, Alex Proyas, Joss Whedon and Zack Snyder. Matthew Vaughn, who cast Kelsey Grammer as Beast and Vinnie Jones as Juggernaut, dropped out during pre-production and was replaced by Ratner. Filming started in August 2005, budgeted at $210 million, the most expensive film at the time of its release. X-Men: The Last Stand received mixed reviews from critics and fans, but grossed approximately $459 million worldwide, the seventh-highest grossing film of 2006.

The pharmaceutical company Worthington Labs announces it has developed an inoculation to suppress the X-gene that gives mutants their powers and makes them different from other humans, offering the "cure" to any mutant who wants it. While some mutants are interested in the cure, including the X-Men's Rogue, many others are horrified by the announcement. In response to the news, the X-Men's adversary Magneto raises an army, warning his followers that the "cure" will be forcefully used to exterminate the mutant race.

Cyclops, still depressed about the loss of Jean Grey, returns to Alkali Lake. Jean appears to Cyclops, and as the two kiss, Jean changes and kills Cyclops. Sensing trouble, Professor Charles Xavier sends Wolverine and Storm to investigate. When they arrive, the two X-Men encounter telekinetically floating rocks, Cyclops' glasses, and an unconscious Jean. Xavier explains that when Jean sacrificed herself, she unleashed the powerful alternate personality she calls "Phoenix". Wolverine is disgusted to learn that Xavier has kept Jean in check telepathically, but when Jean awakens, he realizes she is not the Jean Grey he knew. Jean pleads with Wolverine to kill her, but when he refuses, the Phoenix surfaces and telekinetically slams Wolverine into a wall. She then escapes to her childhood home.

Magneto, also aware that Jean is now a powerful mutant, meets Xavier at Jean's house. The two men vie for Jean's loyalty until the Phoenix resurfaces, unleashing her devastating power. She destroys her family's house, disintegrates Xavier, and leaves with Magneto. Following the loss of Xavier, the X-Men regroup and confront Magneto's army, which is attacking the pharmaceutical company. During the fight, Beast injects Magneto with the "cure", nullifying his mutant powers. After the battle, the Phoenix emerges and begins to destroy everything around her. Momentarily gaining control, Jean begs Wolverine to save her. Telling Jean he loves her, Wolverine reluctantly kills her with his claws.

The school continues without Xavier, with Storm now as headmistress and Logan as a teacher; the President appoints Beast as ambassador to the United Nations; Rogue returns, telling Iceman she has taken the "cure." The underpowered Magneto sits at a chessboard in a park and reaches out toward a metal chess piece that moves slightly, indicating that the mutant cure may possibly be only temporary. Following the end credits, Dr. Moira MacTaggert checks on a comatose patient who greets her with Xavier's voice. Startled, she replies, "Charles?"