25 episodes, each 45 minutes long, are set to be filmed in Glasgow in March, to air on BBC One later in the year.
The comic told The Sun: "I'm chuffed to bits to be back on BBC daytime again with The Answer Run. I really feel like this is going to be one of those addictive TV quiz shows where you're sat at home shouting at the telly because you reckon you could've done better. It's fast-paced, full of jeopardy and requires contestants to be able to make split-second decisions. But I promise we'll have a laugh too."
The new format sees contestants competing in pairs - answering questions "ranging from Beyonce or Barbie to Neptune or Mars, football or basketball and everything in between"- with teams eliminated until one duo remains with a chance to win the cash that has been banked.
Talking about daytime television, Manford says: "It's a market of people who are under-represented - the audience who watch telly during the day. They still need entertaining, and often you almost become part of their day and routine, so I think it's really important."
The star's new stand-up tour, A Manford All Seasons, begins in November.