The deceased were identified as Sajal, 26, son of Humayun Kabir; Sahin, 25, of Lalmoti village in Sadar Dakshin upazila; and Kajal, 25, son of Sadek Hossain of Sanonda village in Lalmai upazila.
The accident took place at Padua Bazar in the city around 12:15pm.
A bus of Shyamoli Paribahan hit the motorcycle, critically injuring the three riders, said Alamgir Hossain, officer-in-charge of Mainamati Highway Police Station.
Later, locals took them to Comilla Medical College Hospital where doctors pronounced them dead.
Police arrested bus drive Aminul Haque and seized the bus.
A case will be filed over the incident, the OC added.