The chef took on the site with the help of investors last month, after stepping down as chef director of D&D London’s 20 Stories.
Manchester House closed and entered administration in October, which its then-owner Living Ventures blamed on a period of 'difficult trading'.
Restaurant MCR will relaunch this week, offering a choice of a six or 12-course tasting menu, and an express lunch of three or six courses.
Byrne told the Manchester Evening News the menu was an ‘evolution’ of his previous cooking at Manchester House, which he oversaw from its 2013 launch until 2017.
He has also reduced the number of covers and says he wants the restaurant to feel more ‘cosy and homely’, with less pressure to turn tables.
The site will close for a complete refit in August 2019.
"While it’s been a crazy week turning this around...it means that we can bring back the tasting menu and get back to basics," says Byrne.
"Doing what I love, sending food and watching as our customers connect with the food.
“While we are focused on delivering an experience and the 12 course tasting menu, the key ingredient for the new restaurant is putting the guest at the heart of everything we’re doing. If our guests want something other than what is on the menu, if we have the ingredients then we can make it work for them.”