It happened just after 11:30 p.m. Tuesday at the Philly Bar and Restaurant in Northeast Philadelphia.
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The bar is in a shopping center - where the NetCost Market is located - on Welsh Road near Roosevelt Boulevard.
A witness told Action News that a group of men interrupted a game of pool and that the situation got heated.
Police said employees tried to kick three men out of the bar who were causing a disturbance, but one had to be forced out.
Family members identify woman killed after man fires into bar
The man then walked to a pick-up truck, about 200 feet away, and fired 15 shots into the bar, police said.
All three men left the scene in the truck, which is described as black or dark in color.
Investigators said five of the bullets went through the front window, and one struck Jailene Holton, 21, in the head.
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Police said she was hanging out with friends when they saw her fall to the ground.
"She was not part of the disturbance. She was not an employee. She was just a customer and she was with friends," said Chief Inspector Scott Small.
"Matter of fact, she was not even anywhere near the front window where the bullets went through," Small continued. She was further at the back of the bar and she was just spending time with her friends when she got struck by stray gunfire."
Police and medics found her on the floor in the back of the bar and rushed her to Jefferson Torresdale Hospital.
Holton was taken into surgery but was pronounced dead a short time later.
James Holton, Jailene's uncle, said she was a good kid and was acting as the designated driver.
"She didn't go out often. Her friend called her up, she went out to Topgolf and then they came (to the Philly Bar and Restaurant). They were only going to be there for about 15 to 20 minutes and that's when the altercation broke out and whatever this guy started shooting," James Holton said.
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Her family now joins many others who are grieving the loss of loved ones due to gun violence in the city.
"When are people going to get fed up with reckless shooting in this city? Nobody does nothing. You get a mouthpiece for 20 seconds on TV and that's it," said Holton. "Everybody's running around like it's the wild west out here. Cowards shooting at a bar from 150 feet or more. Somebody goes out for 10 or 15 minutes and then they're dead. How's that fair? How many children got to die before people say enough is enough?"
Sean Fabian, who worked with Holton, said he's devastated.
"I started crying a little bit. You hear about all these shootings in Philly, shooting in Texas, New York, it doesn't really hit until it happens in your neighborhood," he said.
A second victim was struck by glass and suffered a cut to his face when bullets went flying through the bar windows, police said.
Police are reviewing surveillance video and speaking with nearly two dozen customers and employees as they work to get a better description of the man and the truck.
Anyone with information is asked to call police at 215-686-TIPS.
RELATED COVERAGE: Building it Better Together series on Gun Violence Solutions