While Milla Jovovich's Alice appeared to sign off in her final movie, she can still return for a new Resident Evil. When Paul W.S. Anderson signed on to direct 2002's Resident Evil movie, he was already a big fan of the video game series. That said, he felt if he brought in game characters like Jill Valentine or Chris Redfield, viewers would already know they make it out alive and thus there would be little tension. For this reason, he created a new cast of characters for his Resident Evil, fronted by Milla Jovovich's Alice.
When Resident Evil begins, Jovovich's Alice awakens in an abandoned mansion with no memory of who she is or how she got there. As the story progresses, her dormant combat skills keep her alive against hordes of zombies and a murderous A.I. dubbed The Red Queen. Resident Evil could just about function as a prequel to the original game, but as the sequels arrived, it very much became its own distinct franchise. Jovovich emerged as a new action star, with each sequel seeing her perform more and more outrageous stunts. Alice has yet to appear in any Resident Evil games, but she's still one of the most famous characters in the franchise.
In all, Milla Jovovich's Alice led six Resident Evil movies, closing out with 2017's The Final Chapter. This brought her story full circle, where she discovers she's a clone of one of Umbrella's co-founders, who orchestrated an apocalypse to "cleanse" the planet so they could re-emerge and rebuild in the aftermath. Resident Evil: The Final Chapter's ending saw Alice destroy the last remnants of Umbrella and releasing an anti-virus into the atmosphere that should wipe out the monsters the company unleashed. The franchise was supposed to be rebooted with 2021's Resident Evil: Welcome To Raccoon City, which started a new canon unreleased to Jovovich's era, but the movie was a box-office dud. With this in mind, it's still possible for Jovovich's Resident Evil series to continue.
The planet took a major beating throughout Paul W.S. Anderson's Resident Evil cycle, and by the time of The Final Chapter, the Red Queen claimed there were less than 5,000 people still living. Resident Evil: The Final Chapter did, on the surface, provide resolution to Alice's story, but the final sequence left the door wide open for more adventures. Milla Jovovich's Alice gives a voiceover revealing it would take years for the anti-virus to fully sweep the planet, and the ending saw her arrive in a post-apocalyptic Manhattan to seek out more survivors.
During the release of Resident Evil: The Final Chapter, both Jovovich and Anderson stated they were finished with the saga and were ready to move on. However, their next collaboration Monster Hunter - an adaptation of another hit Capcom video game - didn't land at the box office and the success of Jovovich's Resident Evil seems to have doomed Welcome To Raccoon City's attempt to switch back to horror. Jovovich has since stated she would consider returning as Resident Evil's Alice once again, so the next movie could easily take the form of a legacy sequel. Alice could roam the land like Mad Max helping communities fight off surviving creatures or bandits while meeting new characters from the games. Given that audiences didn't take to the 2021 reboot, the producers might even favor the return of Milla Jovovich's Resident Evil series, which is still the most successful game to movie series to date.