Keanu Reeves has already denied Marvel 3 times:
Captain Marvel (2019):
The villain Yon-Rogg, who was eventually played by Jude Law in Captain Marvel, was almost played by Reeves, but he was in the middle of filming John Wick 3: Parabellum.
Spider-Man: No Way Home (2019):
Marvel also offered Reeves a role in this film, however, although he was excited, he turned it down due to scheduling conflicts.
Reeves was tipped for a nondescript role in the film The Forever, which would see him opposite Angelina Jolie. However, he had to refuse it, also due to scheduling conflicts, as he was committed to other projects.
In a recent interview, Kevin Feige revealed: “I don’t know when or if [Keanu Reeves] will appear on MCU, but we really want to find the right way to make that happen.”