In May, the 85-year-old filmmaker - who funded the $120 million project himself - was accused of pulling women to sit on his lap and trying to kiss a string of topless or scantily clad female extras during filming for a nightclub scene.
Speaking to Rolling Stone magazine, he described the original report in The Guardian newspaper as "totally untrue".
He added: "The truth of the matter is, they were looking for some sort of dirt.
"The young women I kissed on the cheek, in regards to the New Year's scene, they were young women I knew...
"It's all so ridiculous. Look at the timing of that article. It's right before we're about to premiere the film at Cannes. They're just trying to damage the picture."
He insisted someone wanted to hurt his movie because he doesn't "follow rules" set by Hollywood.
He argued: "There's a prevailing tendency in Hollywood to say, if you follow our rules, you'll have a better chance of a success.
"'Well, what about Francis? He doesn't follow your rules.' 'Well, look, what's going to happen to him, he's going to have a failure'.
"I'm trying to do something different here. Film is change. I mean, the movies that your grandchildren are going to make are going to be nothing like what we see now."
Francis has been defended against the claims he acted inappropriately on the set of his latest film by its executive co-producer Darren Demetre.
He told The Guardian in the same report that carried allegations of Francis' apparent misbehaviour on set: "I was never aware of any complaints of harassment or ill behaviour during the course of the project.
"I have known and worked with Francis and his family for over 35 years.
"As one of the first assistant directors and an executive producer on his new epic, 'Megalopolis', I helped oversee and advise the production and ran the second unit.
"Francis successfully produced and directed an enormous independent film, making all the difficult decisions to ensure it was delivered on time and on budget, while remaining true to his creative vision.
"There were two days when we shot a celebratory Studio 54-esque club scene where Francis walked around the set to establish the spirit of the scene by giving kind hugs and kisses on the cheek to the cast and background players.
"It was his way to help inspire and establish the club atmosphere, which was so important to the film.
"I was never aware of any complaints of harassment or ill behaviour during the course of the project."
Francis' 'Megalopolis' premiered at this year's Cannes Film Festival on 17 May.
The director first began writing the project in 1983, and sold a portion of his wine empire in 2021 to self-fund the $120 million project.