Frixione was born in Genoa, and educated in his native city at the Accademia Ligustica of Finea Arts, which he attended from 1859 to 1866.
In 1901 he was awarded as a Knight of the Order of the Crown of Italy by King Vittorio Emanuele III.
Frixione's paintings, often of small size, are characterized by a quiet atmosphere of peace and serenity, and almost a reluctance to express his feelings on the canvas.
The spiritual aspect of the artist is evident in some works of religious nature (Christian) carried out mainly with paintings on carved wood.
As an engraver he concentrated mainly on portraits; among his subjects were St Francis Maria of Camporosso (1804–1866), the violinist Ernesto Camillo Sivori (1815–1894) and Margaret of Savoy (1851–1926).