Bettis spent the entire 2016 season in the Rockies' starting rotation, pitching to a 4.79 ERA in 189 innings pitched. In early December 2016, Bettis was diagnosed with testicular cancer. After undergoing surgery to remove a testicle, he expected to make a full recovery during the offseason. In March 2017, he revealed that the cancer spread, and required chemotherapy.
On August 14, 2017, Bettis made his first appearance in the majors since being diagnosed with cancer, pitching against the Atlanta Braves. He pitched 7 scoreless innings, struck out two, and gave up 6 hits. He was placed on the disabled list on July 3, 2018, with a blister injury.
Bettis and his wife, Kristina, had a daughter in April 2017.