Colombo, who had previously designed Alfa Romeos for Enzo Ferrari, placed bore centres at 90 mm apart, allowing for significant expansion.

Significant updates were made in 1963 for the 330 series, featuring a redesigned block with wider, 94 mm, bore spacing.

Although the Lampredi V12 was a real force for the company, it was Colombo's engine which powered Ferrari to the forefront of high-performance automobiles through the 1950s and 1960s.

The first Ferrari-designed engine was the 1,496.77 cc (1.5 L; 91.3 cu in) V12 125, the work of Gioacchino Colombo and assistants Giuseppe Busso and Luigi Bazzi [it].

Colombo and Ferrari had designed the engine with Formula One regulations in mind, and introduced it the next year in the company's first F1 car, the 125 F1.

However, the single-stage Roots-type supercharger was incapable of producing the high-end power required to compete with the strong eight-cylinder Alfa Romeo 158 and four-cylinder Maserati 4CLT.

Development continued the following year, but the problematic superchargers were dropped in favor of larger displacement and Lampredi's 275 engine superseded the original Colombo design.

Beginning with the famous 250 TR, "Testa Rossa" racing car, Ferrari began a new series of modifications to the Colombo 250 engine.

In a departure from previous Ferrari designs, the valve angle was reduced three degrees to 54° for a more-compact head.

The 330 Colombo engine was enlarged with an 81 mm (3.19 in) bore to 4,390.35 cc (4.4 L; 267.9 cu in) for 1966's 365 California, retaining single overhead cams and wet sump lubrication.