The design failed to mature even after years of intensive development and several major design changes. The Bomber B program failed along with it, leaving the Luftwaffe with hopelessly outdated designs during the second half of the war. Only a small number of 222s were built, less than 300. They never left the prototype phase, but the design nevertheless continued appearing on proposals for new Luftwaffe multi-engined designs long after most had given up hope it would ever work..
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Since the Junkers Jumo 222 has six cylinder banks, it is one of the so-called Hexagon engines. Other examples of hexagon engines are rare - for example, the 24-cylinder water-cooled Dobrynin VD-4K and the 12-cylinder air-cooled Curtiss H-1640 Chieftain. Analogously, there were also octagon engines such as the Bristol Hydra with eight cylinder banks.
Design work on the Jumo 222 started in 1937. The engine was configured with six inline cylinder banks spaced at equal angles
The Colombian Air Force used three Ju 52/3mde bombers equipped as floatplanes during the Colombia-Peru War in 1932–1933.