All the passengers on the bus were released unharmed after the attack.
The incident took place on a stretch of motorway in the province of Alessandria, some 60 miles (90km) northeast of the city of Turin.
Reports said that, after releasing the passengers, the hijackers set the vehicle alight using petrol canisters.
Police, who set up roadblocks on the motorway, said they had captured two of the men and were looking for the third.
The men were originally believed to be of North African origin but police later said that the two arrested men were Albanian. (Insert the "M" word)
The bus, travelling towards the town of Novara, was between the towns of Alessandria and Acqui Terme when the incident occurred.
The three men, reported to be armed with knives and a gun, boarded the bus and ordered the driver to turn around.
Some 20 people, most of them students, were on the bus at the time of the attack.
When the bus arrived in the city of Alessandria, all the passengers were ordered off the bus.
One of two off-duty policemen on the bus intervened to try to stop the men and suffered a minor knife injury during the incident.
Italian media reported that there was an exchange of gunfire with police before the men set the vehicle alight and abandoned it at Trecate, on the outskirts of Novara.