It happened just before midnight on Clovis Avenue and Huntington Boulevard.
Fresno firefighters arrived to find three people injured with burns; two of them had scrapes.
Officials say the victims were inside the building when the flames blocked their way out. They had to escape through a window.
Investigators say there were no utilities connected to the structure. The fire is believed to be tied to homeless activity on the property.
Firefighters searched and confirmed there was no one else in the building.