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Jim Carrey and Jeff Daniels return to star in the adventures of the two dumbest idiots in cinema after the success of the first film. This time they are directed again by Bobby and Peter Farrelly. Twenty years have passed since Harry and Lloyd met and formed the funny duo that made us laugh with their crazy ideas, but neither of them seems to have matured. Now, Harry has been diagnosed with a kidney problem and needs a transplant. At the same time, he discovers that he has a daughter that he barely knows and decides to go find her to ask her to donate one of her organs. For this adventure he will need the help of his inseparable Lloyd. However, he is not in very good physical or psychological condition since Mary rejected him. Harry will have to prepare him before living numerous adventures during the trip.