The former Late Late host is to present a brand new religious series called The Meaning of Life.
And the first episode will see him question the film star about the events in his life which have shaped his beliefs about faith, spirituality and the bigger picture.
The interview will mark Farrell's most intimate sit-down chat since his infamous appearance on BBC's Friday Night with Jonathan Ross last October, in which he admitted he "was dying" prior to a rehab stint in 2005.
Farrell described himself as "fairly drunk and high for 16 years" before revealing how he checked into rehab for five weeks.
Speaking at the time he said: "I came back into the world and everything was in a degree of focus that I hadn't experienced.
"Desperation will allow you to do incredible things in the name of survival.
"So much of the work that I did I was struggling so hard to keep it together. A lot of my energy was going into trying not to have a complete meltdown. By the end of Miami Vice I was just done," he said.
The Castleknock native went on to explain what had caused his spiral into drugs and alcohol addiction.
"I don't believe I have any chemical predisposition towards depression, but let's just say I was suffering from a spiritual malady for years and I indulged it," he revealed at the time.
Well known for his interviewing skills, Byrne (75) is sure to delve deeper into the topic when he asks Colin the questions: What's it all about? Why am I here? Is there a God? and Why do bad things happen?
The long-time broadcaster is also set to interview Sinn Fein leader Gerry Adams about his faith for the new series.
Discussing the interview earlier this week Byrne said: "I disagree with everything he [Gerry Adams] stands for, everything the Provisional IRA stands for and everything Sinn Fein stands for.
"Nonetheless, I have great regard for Gerry Adams, himself in his person. I think he is a very impressive guy and a very impressive communicator who has a wonderful way with words," he told a Sunday paper.
The much-respected RTE man went on to explain how his latest meeting with Adams had been friendly and completely without confrontation.
Although he admits: "It was an interview where you certainly had to think on your feet."
The first episode will air on Sunday, April 19 at 10.20pm featuring Colin Farrell. A screening date for the Gerry Adams interview has yet to be announced.