"I'm not gonna do it and I'm not gonna be asked and it's not gonna happen," he said in an interview to air Thursday on CBS "This Morning."
Bush has routinely beat back rumors that he could be tapped as a Republican vice presidential pick. He flirted with a presidential bid last year, and his name was often floated during this year's Republican primary as a potential late-entry candidate.
The former governor, however, said while he's not making a bid in 2012, he has yet to make up his mind on a future run.
"I've not made that decision," he said, though he admitted this year's "window of opportunity" was "probably my time."
"Although, I don't know, given what I believe and how I believe it, I'm not sure I would have been successful as a candidate, either," he added, without elaborating on his doubts about a potential run.
Asked about calls from those within the GOP for Bush to launch a presidential campaign this year, he said he tries not to look back on what could have been.
"That's pure speculation. And one thing I know for sure is you don't. you don't worry about 'could have, would have'," he said. "You focus on the things that you can control, and that's what I'm doing."