The world has been consumed by the T-Virus and Umbrella develops clones of Alice in hopes of finding one who displays Alice's powers. Elsewhere, Claire Redfield (Ali Larter) leads a convoy of survivors across the Nevada desert, including Racoon City survivors Carlos Olivera and L.J. Wayne (Mike Epps) along with K-Mart (Spencer Locke), Nurse Betty (Ashanti) and Mikey (Chris Egan). A secluded Alice roams the country for survivors, after failing to find any living people, she comes into contact with Claire's convoy after she rescues them from mutated crows.
The convoy, along with Alice, heads to Las Vegas to gather supplies so they can reach Alaska, a place called Arcadia thought to be a safe haven. Whilst there, they are attacked by super zombies who kill most of the convoy. After being bitten earlier, L.J. transforms into a zombie and infects Carlos. Isaacs himself is bitten by a super zombie and injects himself with large doses of the Anti-Virus which transforms him into a Tyrant. Claire and K-Mart leave for Alaska in an Umbrella chopper, whilst Carlos sacrifices himself in an explosion to aid their escape. Alice confronts Isaacs, in Tyrant form, in the underground Umbrella station. After his defeat, Alice looks on with a clone of herself into a room full of pods as thousands of clones awaken.
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