The Argentina global has now scored 27 league goals - more than anyone else in Europe's top five leagues this term.
Betis were looking every bit as threatening as their visitors, though, and it took some fine last-ditch defending from Barcelona to keep them at bay shortly before the half-hour mark as they peppered the box with risky crosses.
Barca return to action following the global break with a Catalan derby at home to Espanyol on March 30, while nearest title rivals Atletico Madrid, who are 10 points behind, visit Camp Nou a week later.
Messi completed his hat-trick shortly afterwards, playing a one-two with Rakitic before producing an exquisitely impudent chip over Lopez and off the underside of the crossbar before going in - a fitting way to end the game.
Luis Suarez, whose superb flick set up Messi's second, scored his own brilliant goal after a scintillating solo run but it was ultimately reduced to a footnote, in what became another night all about his Argentinian partner. Betis are a side that treat the ball well. But even for him, the sight of the Real Betis fans were applauding by the end tugged on the heartstrings.
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The ball was laid back to him just inside the box; a position where most players would put their foot through the ball and power an effort at goal.
Argentine football legend Lionel Messi was in the best form of his life scoring three goals for the Catalans in this encounter. Messi sent his strike around the wall and into the top corner of the net, leaving Lopez little chance.
Barca's win was tainted by a late injury to Suarez, however.
The result sees Barca take another giant stride towards defending their La Liga crown and keeps them firmly on course for a potential treble this season. He scored three goals and could have scored a fourth.