Borisenko launched for a second time on 19 October 2016 aboard Soyuz MS-02 as Flight Engineer, launch was originally scheduled for 23 September although was delayed due to technical issues with the spacecraft.
Borisenko and his two crew mates, Roscosmos cosmonaut Sergey Ryzhikov and NASA astronaut Shane Kimbrough rendezvoused and docked to the ISS on the 21st of October following a two-day rendezvous, and officially joined the Expedition 49 alongside Russian commander Anatoli Ivanishin and flight engineers Takuya Onishi of JAXA and Kathleen Rubins of NASA. Due to month long launch delay Soyuz MS-02 faced, the hand over period was short, Expedition 49 ended on 30 October 2016 when Ivanishin, Onishi and Rubins returned to Earth aboard Soyuz MS-01, leaving the MS-02 trio on board the ISS as Expedition 50 with Kimbrough taking command.
The rest of the Expedition 50 crew joined Borisenko and his two crew mates on 19 November 2016 when Soyuz MS-03, carrying Russian cosmonaut Oleg Novitsky, French astronaut Thomas Pesquet, and NASA astronaut Peggy Whitson docked to the station. During the Expedition the Russian Orbital Segment of the ISS was supposed to welcome the Progress MS-04 uncrewed resupply spacecraft, although the spacecraft failed to reach the ISS due to an issue with the Soyuz-U launch vehicle's third stage which shutdown sooner than intended. Progress flights quickly resumed during Expedition 50, with the launch of Progress MS-05 in February 2017.