Renfree attended Notre Dame Preparatory High School in Scottsdale, Arizona, where he was a four-year letterman in football. He was voted as the team's "Most Valuable Player" his junior and senior year. In his junior year, Renfree, threw for 2,483 yards and 25 touchdowns with five interceptions. Before the start of his senior year Renfree was invited to the 2007 Elite 11 Camp along side future NFL quarterbacks Andrew Luck, Blaine Gabbert, Mike Glennon, Landry Jones, and EJ Manuel. As a senior, he completed 197 of 357 passes for 3,353 yards and 41 touchdowns with just six interceptions. Renfree finished off his high school career by completing 23 of 33 passes for a state championship game record 411 yards and five touchdowns against Cottonwood Mingus. He was named Arizona's Big School Class 5A and 4A Player of the Year and to the All-Arizona team as a senior by The Arizona Republic.He was also named to the Parade All- American High School Football team in his senior year in 2008.
As a freshman in 2009, Renfree played in five games as a backup and completed 34 of 50 passes for 334 yards, four touchdowns, and two interceptions. While playing in the fourth quarter against Georgia Tech Renfree suffered from a torn ACL and was forced to miss the remainder of the 2009 season. In 2010, Renfree started 11 of 12 games, and was the recipient of the Carmen Falcone Award as Duke's Most Valuable Player. On the season, he completed 285 of 464 pass attempts for 3,131 yards with 14 touchdowns and 17 interceptions. In 2011, serving as a team captain, Renfree started all 12 games and completed 282 of 434 pass attempts for 2,891 yards with 14 touchdowns and 11 interceptions. This set the Duke single-season record for pass completion percentage. In 2012, Renfree completed 297 of his 442 passes for 3,113 yards, 19 touchdowns and 11 interceptions. He ended his career owning or sharing 14 school records and earned the team's Carmen Falcone MVP award for a second time. He sustained a torn right pectoral muscle in his right (throwing) arm on the last play of Duke's last game (Belk Bowl) requiring surgical repair and, as a result, was unable to participate in the NFL combine or Duke's Pro Day hurting his draft stock.
In recognition for his athletic and academic performance in 2012, Renfree was the recipient of several prestigious awards including the ACC's Jim Tatum Award, National Football Foundation Scholar Athlete Award, and Pop Warner National College Football Award. He was also named a finalist for the William Campbell Trophy, which is considered the "Academic Heisman" in college football.
On April 27, 2013, Renfree was drafted in the seventh round (249th overall) by the Atlanta Falcons of the National Football League. He signed with the team on July 24. Terms were undisclosed. On August 27, 2016, Renfree was waived by the Falcons.
On January 30, 2017, Renfree signed a reserve/future contract with the Tampa Bay Buccaneers. He was released by the Buccaneers on May 19, 2017, after the team signed veteran quarterback Ryan Fitzpatrick.
Renfree is the oldest of three brothers. His youngest brother, Charlie, plays football as a center at the University of Wyoming. Renfree's father played linebacker at the University of Notre Dame and is currently an orthopedic surgeon at the Mayo Clinic Hospital in Scottsdale.