"It's over," the New York Daily News quoted Franco as telling Playboy for its upcoming August issue.
"We'd been living together in LA and then came to New York to go school for two years," Franco said. "Then I signed up for more school at Yale. I think that was it for her."
UsMagazine.com noted Franco has been pursuing multiple degrees at Yale, Columbia and New York universities while juggling his busy acting career.
Franco's films include "127 Hours" and "Pineapple Express." He was also a cast member of the TV series "Freaks and Geeks."
O'Reilly will be seen soon in the movie "The Help."