Poor Rex Ryan.

Poor, poor Buffalo Bills.

Do they know what it means to be facing a double dose of New England Patriots wrath?

It’s bad enough that the Bills are up next on the Tom Brady revenge tour. The four-time Super Bowl-winning quarterback has put up some ridiculous passing numbers since returning from his four-game DeflateGate suspension, and the Patriots are 3-0 in those games. It’s looking decidedly like their romp to a 16-0 regular season in 2007 in the aftermath of the Spygate scandal, when the rest of the NFL was made to pay – at least until the Super Bowl – for what the Patriots perceived as an injustice.

As if that’s not enough, the Patriots also seek to avenge their only loss of the season. And it was an ugly defeat, a 16-0 decision to the Bills in Foxborough, Massachusetts, earlier this month in the final game of Brady’s suspension with rookie Jacoby Brissett at quarterback.

Beating a Bill Belichick-coached Patriots team twice in the same season is not impossible. But doing it twice in the same regular season has been next to impossible for New England’s AFC East foes.

Eight times a team has beaten Belichick’s Patriots twice in a season, including last year when Denver beat them in the regular season and the AFC title game.

On five other occasions a team has beaten the Belichick-coached Patriots twice in a season with one of the victories coming in the postseason: the Baltimore Ravens in the 2012 season, the New York Giants in the 2011 season (with the second triumph coming in the Super Bowl), the New York Jets (coached by Ryan) in the 2010 season, the Indianapolis Colts in the 2006 season and the Broncos in the 2005 season.

But only twice has it happened in the same regular season. That goes all the way back to Belichick’s first season as head coach of the Patriots in 2000. New England went 5-11 and lost twice each to the Jets and the Miami Dolphins. That was the AFC East’s last chance to beat up on Belichick and the Patriots.

Belichick and Brady won their first Super Bowl in tandem the following season, and the Patriots have dominated the division and the league since then.

Brady has been oh-so-sharp since his return. He has thrown for 1,004 yards and eight touchdowns, without an interception, in victories over Cleveland, Cincinnati and Pittsburgh. He has a passer rating of 132.6. He not only could win the league’s most valuable player award while playing in only 12 games; he could be a no-doubt-about-it MVP if this continues.

It is a far, far different challenge for the Bills than when they shut out the Brissett-led Patriots a few weeks ago. Tight end Rob Gronkowski had one catch for 11 yards in that game. He has 16 catches for 364 yards and two touchdowns in three games with Brady back in the lineup.

Buffalo could be without tailback LeSean McCoy on Sunday because of a hamstring injury. But give this much to the Bills: They don’t back down from the Patriots. Several Bills defensive backs were fined for their roles in a relatively minor pregame scuffle prior to the Oct. 2 game in Foxborough, precipitated when Brissett jogged through the area where the members of the Buffalo secondary were warming up while on his way back to the locker room.

This week, Bills players said a similar provocation this weekend would bring a similar response, fines or not. It fits right in with Ryan’s past comment that he’s not around merely to kiss Belichick’s rings.

But Ryan isn’t playing up that aspect of the rematch.

“Trust me,” he said this week, “I’m not worried about that. We’re here to play a game and that’s it.”

Facing Brady this time changes everything, Ryan acknowledged.

“As many years, as many games as we’ve played against each other,” Ryan said, “we’ve probably tried everything known to man” against Brady.

And that’s why the Bills have at least an anything-can-happen chance Sunday. They are, like their coach, wildly unpredictable. Their 2016 season seemed all but done before it really even started when they lost their first two games to the Ravens and Jets, and fired offensive coordinator Greg Roman. Next up on the schedule were the Arizona Cardinals and the Patriots, and an 0-4 start appeared likely. There was plenty of talk about Ryan’s job security.

So what did the Bills do? They beat the Cardinals. They beat the Patriots. That was part of a four-game winning streak and all seemed well. But unable to live with such prosperity, the Bills allowed 214 rushing yards by Dolphins tailback Jay Ajayi and lost 28-25 last Sunday at Miami. So they would be merely a .500 team at 4-4 if they can’t beat the Patriots on Sunday.

It makes for plenty of intrigue this weekend.

“Obviously we’ve got a big challenge in front of us,” Ryan said. “We recognize that.”